Bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs) synthesis, reduces neointimal formation in animal models of vascular injury and recently has been shown to inhibit in-stent late loss in a placebo-controlled phase II clinical trial. However, the mechanisms underlying the efficacy of bindarit in controlling neointimal formation/restenosis have not been fully elucidated. The...

Both type 1 and type 2 diabetes are associated with increased risk of cardiovascular disease. This is in part attributed to the effects of hyperglycemia on vascular endothelial and smooth muscle cells, but the underlying mechanisms are not fully understood. In diabetic animal models, hyperglycemia results in hypercontractility of vascular smooth muscle possibly due to increased activation of Rh...

Human blood platelets contain two proteins very similar in structure and function to the contractile proteins of muscle: actin and myosin. Platelet actin has a similar molecular weight (43 000 daltons) and amino acid composition to muscle actin. It polymerizes into long filaments which can form ‘arrowheads’ with skeletal muscle and platelet myosin subfragment-1 (S-1) as viewed in the electron m...

To identify regulatory mechanisms potentially involved in formation of actomyosin structures in smooth muscle cells, the influence of F-actin on smooth muscle myosin assembly was examined. In physiologically relevant buffers, AMPPNP binding to myosin caused transition to the soluble 10S myosin conformation due to trapping of nucleotide at the active sites. The resulting 10S myosin-AMPPNP comple...

Fesselin is a proline-rich actin binding protein that has recently been isolated from smooth muscle [Leinweber, B. D., Fredricksen, R. S., Hoffman, D. R., and Chalovich, J. M. (1999) J. Muscle Res. Cell Motil. 20, 539-545]. Fesselin is similar to synaptopodin [Mundel, P., Heid, H. W., Mundel, T. M., Krüger, M., Reiser, J., and Kriz, W. (1997) J. Cell Biol. 139, 193-204] in terms of its size, is...

BACKGROUND & AIMS SRF (Serum Response Factor), a widely expressed transcription factor, controls expression of mitogen-responsive and muscle-specific genes, thereby regulating the contractile actin microfilament. Genetic Srf deletion studies showed SRF to be indispensable for in vivo skeletal and cardiac muscle cell development. We now investigated for the first time in vivo SRF functions in sm...

Pectenotoxin-2 (PCTX-2) is one of the polyether macrolide toxins isolated from scallops involved in diarrheic shellfish poisoning via actin depolymerization. In the present study, we examined the bioactive mechanism of PCTX-2 in smooth muscle cells and clarify mode of action of the PCTX-2-induced actin depolymerization using purified skeletal actin. PCTX-2 (300 nM-3 µM) non-selectively inhibite...

Although altered renal vascular reactivity is known to occur after ischemia, the structural basis explaining the phenomenon has not been clarified. To evaluate for structural damage to the renal vasculature in ischemic acute renal failure (ARF), F-actin in the renal vasculature of rat kidneys and cultured vascular smooth muscle cells was examined using confocal fluorescence microscopy. The left...

Hypertrophy of rat urinary bladder smooth muscle was induced by partial urethral obstruction. Bladder weight increased from 70 to 240 mg after 10 days and to 700 mg after 7 wk. Removal of the obstruction after 10 days caused a regression of bladder weight to 130 mg. The relative volume of smooth muscle in the bladder wall increased during hypertrophy. The concentration of myosin in the smooth m...

The distribution of contractile and cytoskeletal proteins in smooth muscle has been mapped by immunocytochemical methods, with special reference to the localization of the actin-binding protein, filamin. Immunolabeling of ultrathin sections of polyvinylalcohol-embedded smooth muscle distinguished two domains in the smooth muscle cell: (a) actomyosin domains, made up of continuous longitudinal a...